The major aims of this proposal are to further characterize the toxicity and carcinogenic potential of polybrominated biphenyls (PBB). Structure-activity relationships will be studied for both toxicity and carcinogenicity. We will therefore be able to determine if there is a relationship between the carcinogenicity and toxicity of polyhalogenated aromatic hydrocarbons. Our hypothesis is that they may not be related for preliminary studies have shown that 2,4,5,2',4',5'-hexabromobiphenyl, a non-toxic PBB congener, can inhibit an in vitro assay for metabolic cooperativity, an activity proposed to be related to tumor promotion. A two-stage initiation-promotion system for studying hepatocarcinogenesis in partially hepatectomized rats will be used. This system should result in a relatively early comparative assessment and evaluation of the carcinogenic potential of the PBB mixture and purified PBB congeners. Altered hepatic foci, neoplastic nodules and hepatocarcinomas will be identified and quantitated by histologic and histochemical methods. Gamma glutamyl transpeptidase activity will be used as a marker for altered foci. We will characterize and compare the histologic, ultrastructural, enzymic and metabolic changes caused by administering the PBB mixture or purified PBB congeners to rats. Emphasis will be on thymic and liver pathology, and upon liver microsomal enzyme induction in evaluation of toxicity. Results of this research will provide means for a better assessment of possible long-term health effects of exposure of people by enabling us to say which of the congeners can be associated with toxicity or with carcinogenicity. By emphasizing structure-activity relationships and by using purified PBB congeners we believe the results of this research will enable us to be better able to predict the health effects of analogous polyhalogenated aromatic hydrocarbons. Therefore, our long-range goal is to show that the structure-activity relationships established for PBB will apply to other polyhalogenated aromatic hydrocarbons.